Highly dispersible antimicrobial and adhesion agents

ABSTRACT

Compositions of matter that have antimicrobial properties and adhesion properties and are highly dispersible in aqueous solutions. The presence of a large number of silanols on the molecules of this invention creates a solubility or disperseability of these molecules in aqueous solutions that is not obtainable from prior art antimicrobial monomers.

BACKGROUND OF THE INVENTION

This invention deals with compositions of matter that have antimicrobialproperties and adhesion properties and are highly dispersible in aqueoussolutions. The presence of a large number of silanols on the moleculesof this invention creates a solubility or disperseability of thesemolecules in aqueous solutions that is not obtainable from prior artantimicrobial monomers. The inventors herein are not aware of any likemolecules in the prior art.

THE INVENTION

Thus, what is disclosed and claimed herein is a composition of matterhaving the average general formula:

wherein the average molar ratio of x:y:z is 0.25-3:4:0.25-3, with theproviso that there is present at least one RSi— unit and at least oneR′Si unit and W is independently selected from the group consistingessentially of Si, Ti, and Zr, and Al, wherein R is a core functionalitybased on the chemistry selected from the group consisting of glycidoxy,amino, acrylamide, methacrylamide, acrylate, methacrylate, C₂-C₈alkenyl, mercapto, ester, isocyanato, epoxycyclohexyl, carboxylic acid,and

wherein p has a value of from 1 to 6 and R³ is selected from the groupconsisting of hydroxyl and alkoxy groups having 1 to 4 carbon atoms.

R² is independently selected from the group consisting of hydroxylgroups,

s has a value of about 1 to 5 and y has a value of 4 wherein R¹ isselected from the group consisting of:

i. a sulfonium salt of the formula

Si(R⁵)₂C_(d)H_(2d)S⁺(R⁴)₂X⁻

in which R⁴ is independently an alkyl group or aralkyl group whereinthere is a total of less than 60 carbon atoms in the molecule, R⁵ isindependently selected from the group consisting of hydroxyl groups,

d is an integer of 1 or greater and X⁻ is a water soluble monovalentanion;

ii. an isothiuronium salt of the formula

Si(R⁵)₂C_(d)H_(2d)S⁺C(NH₂)₂X⁻,

wherein R⁵ is independently selected from the group consisting ofhydroxyl groups,

d is an integer of 1 or greater and X⁻ is a water soluble monovalentanion;

iii. a phosphonium salt of the formula

Si(R⁵)₂C_(d)H_(2d)P⁺(R⁶)₃X⁻

in which R⁶ is independently selected from an alkyl group or aralkylgroup wherein there is a total of less than 60 carbon atoms in themolecule, R⁵ is independently selected from the group consisting ofhydroxyl groups,

d is an integer of 1 or greater a X⁻ is a water soluble monovalent anionand,

iv. an amine of the formula

Si(R⁵)₂C_(d)H_(2d)N(H)(D_(d)H_(2d))NH₂

wherein R⁵ is independently selected from the group consisting ofhydroxyl groups,

in which d is an integer of 1 or greater, wherein (WO_(y)) is derivedfrom W(OR⁷)₄ wherein (OR⁷) is independently selected from the groupconsisting of

-   -   i. —OCH₃,    -   ii. —OCH₂CH₃,    -   iii. —OCH(CH₃)₂,    -   iv. —O(CH₂)₃CH₃,    -   v. —OCH₂CH(CH₃)₂,    -   vi. —O(2-ethylhexyl),    -   vii. acetoxy, and,    -   viii. oximo.

DETAILED DESCRIPTION Of THE INVENTION

One method for providing the materials of this invention comprisesproviding the components:

wherein the molar ratio of x:y:z is 0.25-3:4:0.25-3, _(p) and _(q) eachindependently have a value of 2 or less, and co-hydrolyzing thecomponents in the presence of a stoichiometric amount of water, and acatalyst for hydrolysis and condensation.

By careful, controlled hydrolysis of the precursor monomers, one canobtain these materials at very low molecular weights providing a largenumber of silanols on the molecules, the detail of which can be foundinfra in the specification, and in the examples.

The materials have the average general formula

which is derived by the hydrolysis of the silane precursors

in conjunction with the orthosilicate, or orthotitanate,orthorzirconate, or orthoaluminate, having the general formula

(W(OR′′′)₄)_(y),

wherein the molar ratio of x:y:z is 0.25-3:4:0.25-3.

This hydrolysis is carried out using a stoichiometric or nearstoichiometric amounts of water and a catalyst for hydrolysis andcondensation. Stoichiometric amounts of water, or, an amount of watergreater than stoichiometric, results in low molecular weight materials,which is one of the objectives of the method in this invention. Cautionshould be noted for the use of substantially lesser amounts of water asthat will result in a residual amount of alkoxy in the material which isundesirable for purposes of this invention.

It is believed by the inventors herein that the key to this invention isthe use of the molecule (W(OR′′′)₄)_(y) as the third component of thisinvention. W in the case of this invention is independently selectedfrom the group consisting of Si, Ti, Zr, and Al. Preferred for thisinvention is Si and Ti and most preferred is Si.

The (OR″′) group is selected from the group consisting of —OCH₃,—OCH₂CH₃, —OCH(CH₃)₂, —O(CH₂)₂ CH₃, —OCH₂CH(CH₃)₂, —O(2-ethylhexyl),acetoxy, and, oximo. Preferred for this invention are the groups —OCH₃,—OCH₂CH₃, and —OCH(CH₃)₂, and most preferred are the —OCH₃ and —OCH₂CH₃groups. Preferred orthosilicates and orthotitanates for this inventionare Si(OCH₂CH₃)₄ and Ti(—OCH(CH₃)₂)₄.

Stoichiometry is based on the number of hydrolysable groups on thecombined components. The reaction is carried out in the presence of baseor acid, with acid being the preferred catalyst. The acid catalysts arepreferred to be HCl, phosphoric, and acetic acids, with HCl andphosphoric acids being most preferred.

Bases that are useable herein are amines, NaOH, KOH and the like andpreferred for this invention is NaOH. The hydrolysis reaction is carriedout by combining the components in a predetermined ratio and then addingacidic or basic water to the components at a controlled rate to formsilanols from the alkoxy moieties. For some end use applications of theinventive materials, a slightly higher molecular weight (higher numberof silanol reactive groups) is preferred and in this case, the silicatecomponent is treated for a short period of time by acidic or basic waterto cause the silicate component to hydrolyze and condense before theother components are added

By the preferred means, the following reaction sequence is achieved:

No heat is used in this reaction as higher temperatures (in excess ofabout 150° C.) may result in gelation of the reaction mixture. There isa small exotherm from the hydrolysis reaction but the heat is notsufficient to provide problems with the resultant product. No solventsare required in this reaction, but it is within the scope of thisinvention to utilize solvents. It should be noted that the byproduct ofthe hydrolysis reaction is alcohol. Typically, the products of thisreaction do not need filtration.

As mentioned Supra, it is possible to enhance the molecular weight andthereby increase the amount of silanol functionality on the molecule byfirst mildly hydrolyzing the ortho precursor and then adding theremainder of the components.

Thus, a molecule having the following average formula may be obtained:

One can also provide a material having the formula:

by hydrolyzing the components (CH₃O)₃Si(CH₂)₃OOC(CH₃)C═CH₂, 1Si(OCH₂CH₃)₄ and 2 (CH₃O)₃Si(R⁵)₂C_(d)H_(2d)P⁺(R⁶)₃Cl⁻.

A preferred material is

The materials are liquids as prepared. In some cases, if preferred, theby-produced alcohols and any residual water can be removed to provide asolid material, and in some cases the solid material is hard and appearsto be almost crystalline and in some cases, the material is waxy orpaste-like.

These compositions of matter have antimicrobial properties and adhesionproperties and are highly dispersible in aqueous solutions. The presenceof a large number of silanols on the molecules of this invention createsa solubility or disperseability of these molecules in aqueous solutionsthat is not obtainable from prior art antimicrobial monomers. Thematerials of this invention are also suitable for providing adhesion incombination with ionomers, especially glass ionomers.

EXAMPLES

TEOS Tetraethylorthosilicate Z-6070 MTM methyltrimethoxysilane Z-6030MAPTMS methacryloxypropyltrimethoxysilane 8405 N-(trimethoxysilylpropyl)isothiuronium chloride 2417 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane

The tetraethylorthosilicate or tetrabutyltitanate were placed in a 40 mlvial with a magnetic stirring bar. The functional trialkoxy-silane wasadded and allowed to mix for 30 minutes. Water, adjusted with KOH to pH10 or HCl to pH 2, was added dropwise with agitation. This was allowedto hydrolyze for 60 minutes and 24 hours after which the solution wasevaluated for appearance. All weights are in grams. Compound molecularweights were used to calculate the moles and molar ratios of eachcomponent.

TABLE 1 Sample # Mw 1 2 3 4 5 6 7 Z-6030 248 2.48 2.48 2.48 Z-6070 1361.36 1.36 1.36 TEOS 208 2.08 2.08 6.24 2.08 2.08 2.08 6.24 8405 @ 50% in274.8 5.5 5.5 5.5 22 (11) 2.75 5.5 2.75 water (2.75) (2.75) (2.75) waterpH = 10 18 1.8  1.8 1.8 1.8 Moles- 1/1/2 1/1/2 1/3/1 0/1/46070/TEOS/8405 Moles- 1/1/1 1/1/2 1/3/1 6030/TEOS/8405 Solution @ 24soft gel OK clear clear OK OK OK hours OK OK Application, microbial kill99.99

TABLE 2 Sample # 8 9 10 11 12 13 14 Z-6030 248 2.48 2.48 2.48 Z-6070 1361.36 1.36 1.36 TEOS 208 2.08 2.08 6.24    2.08 2.08 2.08 6.24 2417 @ 50%in 324.85 6.5  6.5 6.5 26 3.25 6.5 3.25 MeCl (3.25) (3.25) (3.25) (13)water pH = 10 18 1   1.8 1.8   1.8 1.8 1.8 1.8 Moles- 1/1/1 1/1/1 1/3/10/1/4 6070/TEOS/2417 Moles- 1/1/1 1/1/2 1/3/1 6030/TEOS/2417 Solution @24 2 phase OK OK OK OK OK OK hours miscible Application, microbial kill99.99 

Purpose

The purpose of this study was to evaluate the effectiveness of testmaterials labeled #1 and #8, in killing or reducing Escherichia coli (E.coli). The standard pour plate count test method was used to evaluatePercent Reduction of Colony Forming Units (CFU).

Study Design

The E. coli (lot number 168756) was purchased from Quanti-Cult™ and isderived from original ATCC® stock cultures. They are receiveddehydrated. A viable streak plate was colonized from this culture. Onecolony was transferred to 5 ml of sterile Tryptic Soy Broth (lot #A3303)and incubated overnight.

Antimicrobial activity is determined by comparing results from the testsample to simultaneously run controls or from the T₀. The concentrationof the suspension is determined using serial dilution and plate countsto determine the amount of Colony Forming Units (CFU's)/ml ofsuspension.

The materials tested in this study are described in the Purpose sectionof this report. Sterile 0.3 mM KH₂PO₄ buffer was inoculated to aconcentration of ˜1.0-3.0×10⁵ CFU/ml. A T₀ plate originated from theinoculated buffer for quantification and prepared 1:100 dilution toinsure that viable inoculum was applied in the test system. The testmaterials were formulated in 20×150 ml test tubes. Aliquots of 0.3 gramsof each of the materials (#1 and #8) were added to sterile test tubes.Five ml of Tryptic Soy Broth was added to each tube and the tubesinoculated with 1×10⁵ CFU, E. coli. The materials were incubated for 48hours. T₀of the inoculums was 9.6×10⁴ CFU/ml. One milliliter aliquots ofthe test article inoculums were added to Petri dishes, Plate Count Agaradded and swirled and the plates were incubated at 35° C. overnight.

Results

The results show 16 CFU/ml for material #1 or >99.9% reduction andmaterial #8 had 0 CFU/ml (no growth) or 100% reduction.

1. A composition of matter having the average general formula:

wherein the average molar ratio of x:y:z is 0.25-3:4:0.25-3, with theproviso that there is present at least one RSi— unit and at least one—R¹—Si— unit and W is independently selected from the group consistingessentially of Si, Ti, and Zr, and Al, wherein R is a cure functionalitybased on the chemistry selected from the group consisting of glycidoxy,amino, acrylamide, methacrylamide, acrylate, methacrylate, C₂-C₈alkenyl, mercapto, ester, isocyanato, epoxycyclohexyl, carboxylic acid,and

wherein p has a value of from 1 to 6 and R³ is selected from the groupconsisting of hydroxyl and alkoxy groups having 1 to 4 carbon atoms; R⁷is independently selected from the group consisting of hydroxyl groups,

s has a value of about 1 to 5; y has a value of 4; R¹ is selected fromthe group consisting of: i. a sulfonium salt of the formulaSi(R⁵)₂C_(d)H_(2d)S⁺(R⁴)₂X⁻ in which R⁴ is independently an alkyl groupor aralkyl group wherein there is a total of less than 60 carbon atomsin the molecule, R⁵ is independently selected from the group consistingof hydroxyl groups,

d is an integer of 1 or greater and X⁻ is a water soluble monovalentanion; ii. an isothiuronium salt of the formulaSi(R⁵)₂C_(d)H_(2d)S⁺C(NH₂)₂X⁻, R⁵ is independently selected from thegroup consisting of hydroxyl groups,

d is an integer of 1 or greater and X⁻ is a water soluble monovalentanion; iii. a phosphonium salt of the formulaSi(R⁵)₂C_(d)H_(2d)P⁺(R⁵)₃X⁻ in which R⁵ is independently selected froman alkyl group or aralkyl group wherein there is a total of less than 60carbon atoms in the molecule, R⁵ is independently selected from thegroup consisting of hydroxyl groups,

d is an integer of 1 or greater and X⁻ is a water soluble monovalentanion and, iv. an amine of the formulaSi(R⁵)₂C_(d)H_(2d)N(H)(C_(d)H_(2d))NH₂ wherein R⁵ is independentlyselected from the group consisting of hydroxyl groups,

in which d is an integer of 1 or greater, wherein (WO_(y)) is derivedfrom W(OR⁷)₄ wherein (OR⁷) is independently selected from the groupconsisting of i. —OCH₃, ii. —OCH₂CH₃, iii. —OCH(CH₃)₂, iv. —O(CH₂)₃CH₃,v. —OCH₂CH(CH₃)₂, vi. —O(2-ethylhexyl), vii. acetoxy, and, viii. oximo.2. A composition of matter comprising a composition of claim 1 and anionomer.
 3. A composition as claimed in claim 1 in combination with amodified glass ionomer.
 4. A method of providing adhesion, the methodcomprising providing a composition of claim 1 and combining saidcomposition with an ionomer and thereafter applying said combination toa substrate.
 5. The method as claimed in claim 5 wherein the ionomer isa glass ionomer. 6.-10. (canceled)